Leadless cardiac pacemaker device configured to provide intra-cardiac pacing

ABSTRACT

A leadless pacemaker device configured to provide for an intra-cardiac pacing, including: processing circuitry configured to generate ventricular pacing signals for stimulating ventricular tissue, and a reception device for receiving a sensing signal indicative of an atrial activity, wherein the processing circuitry is configured to detect an atrial event derived from said sensing signal, wherein the atrial event is a valid atrial sense event, where a series of atrial events lie within a range for a normal atrial rate, and/or when the atrial rate variability is within a certain range indicating a regular atrial rhythm, wherein in case a valid atrial sense event is detected, the processing circuitry is further configured to: determine ventricular pacing events according to atrial events, calculate ventricular-atrial time delays, determine a correction value based a measured time delay and the calculated time delay, and adjust the ventricular pacing timing based on the correction value.

CROSS-REFERENCE TO RELATED APPLICATIONS

This patent application claims the benefit of and priority to co-pendingU.S. Provisional Patent Application No. 62/948,854, filed on Dec. 17,2019, which is hereby incorporated by reference in its entirety

TECHNICAL FIELD

The instant invention generally relates to a leadless cardiac pacemakerdevice for providing an intra-cardiac pacing, in particular aventricular pacing.

BACKGROUND

In recent years, leadless pacemakers have received increasing attention.Leadless pacemakers, in contrast to pacemakers implanted subcutaneouslyusing leads extending transvenously into the heart, avoid leads in thatthe pacemaker device itself is implanted into the heart, the pacemakerhaving the shape of a capsule for implantation into cardiac tissue, inparticular the right ventricular wall of the right ventricle. Suchleadless pacemakers exhibit the inherent advantage of not using leads,which can reduce risks for the patient involved with leads transvenouslyaccessing the heart, such as the risk of pneumothorax, leaddislodgement, cardiac perforation, venous thrombosis and the like.

Leadless pacemakers may specifically be designed for implantation in theright ventricle and, in this case, during implant are placed in or onthe right ventricular wall. A ventricular pacing may for example beindicated in case a dysfunction at the AV node occurs, but the sinusnode function is intact and appropriate. In such a case in particular aso-called VDD pacing may be desired, involving a ventricular pacing withatrial tracking and hence requiring a sensing of atrial activity inorder to pace at the ventricle based on intrinsic atrial contractions.

A pacing using atrial tracking is in particular motivated by patienthemodynamic benefits of atrioventricular (AV) synchrony by utilizing anappropriate sinus node function to trigger ventricular pacing,potentially allowing to maximize ventricular preload, to limit AV valveregurgitation, to maintain low mean atrial pressure, and to regulateautonomic and neurohumoral reflexes.

Publications have explored solutions to use modalities to detectmechanical events of atrial contractions, including the sensing ofmotion, sound and pressure. For example, U.S. Publication No.2018/0021581 A1 discloses a leadless cardiac pacemaker including apressure sensor and/or an accelerometer to determine an atrialcontraction timing. As mechanical events generally exhibit a smallsignal volume, signal detection based on mechanical events, for examplemotion, sound or pressure, may be difficult to sense, in particular whenthe leadless pacemaker device is placed in the ventricle and hencerather far removed from the atrium of which contractions shall besensed. In addition, wall motion and movement of blood generated byatrial contractions may not be directly translated to the ventricle, andcardiac hemodynamic signals, such as motion, heart sounds and pressure,are likely affected by external factors such as posture and patientactivity.

European Patent No. 3 218 049 B1 describes a leadless pacemaker devicethat is configured for implantation in a ventricle of a heart of apatient and is configured to switch from an atrio-ventricularsynchronous pacing mode to an asynchronous pacing mode in response todetection of one or more atrial undersensing events.

U.S. Publication No. 2018/0028814 A1 discloses an implantable medicaldevice system operating in an atrial synchronized ventricular pacingmode and switching to an atrial asynchronous pacing mode when pacingmode switching criteria are met. A control circuit of the system detectsa cycle length change between two atrial cycle lengths determined from acardiac signal that includes far-field atrial triggering events. If thecycle length change is greater than a change threshold, the controlcircuit determines if the pacing mode switching criteria are satisfiedsubsequent to detecting the cycle length change.

Generally, if a competent sinus rhythm is available, it is assumed to bepreferable to use the sinus rhythm to control a ventricular pacing raterather than pacing at the ventricle using a rate response mechanism,such rate response mechanism generally causing an adaption of the pacingrate in dependence of personal activity of a patient (for exampleaccording to an accelerometer reading), such that the pacing rate isadapted dependent on whether the patient for example sleeps or isphysically active or stressed. In times, however, where no sinus rhythmis available, due to for example an undersensing or an incompetentsinus, or when higher rate atrial arrhythmias are present, a pacingaccording to the sinus rhythm is no longer suitable, such that anotherpacing strategy, such as a pacing according to a rate responsemechanism, is to be chosen.

Hence, at different times and conditions different pacing modes may haveto be applied, making a switching between different modes necessary.

The present invention is directed toward overcoming one or more of theabove-mentioned problems, though not necessarily limited to embodimentsthat do.

SUMMARY

It is an object to provide a leadless pacemaker device and a method foroperating a leadless pacemaker device allowing, in particular, for asensible switching between different pacing modes, in particular toadapt a ventricular pacing to a detected atrial sense rate.

Such desires are addressed by a leadless cardiac pacemaker deviceconfigured to provide for an intra-cardiac pacing and having thefeatures of claim 1.

In an aspect of the present invention, a pacemaker device configured toprovide for an intra-cardiac pacing, the leadless pacemaker devicecomprising:

-   -   a processing circuitry configured to generate ventricular pacing        signals for stimulating ventricular, and    -   a reception device for receiving a sensing signal indicative of        an atrial activity, wherein the processing circuitry is        configured to determine an atrial sense rate of atrial events        derived from said sensing signal,    -   wherein in case a valid atrial sense rate is determined, the        processing circuitry is further configured to:        -   determine a ventricular pacing rate according to the atrial            sense rate based on a calculated atrial-ventricular (AV)            delay,        -   Generating at least one ventricular pacing signal at the            ventricular pacing rate,        -   determine a calculated ventricular-atrial delay (VA_(calc))            indicative of a time delay at which an atrial event (As) is            predicted to occur following a prior ventricular event (Vs),        -   measure a true occurrence of a time delay at which an atrial            event (As) occurs following a prior ventricular event (Vs)            (VA_(true)) and determine a correction value (CV) based on a            timing relation between VA_(true) and the calculated            ventricular-atrial delay (VA_(calc)), and        -   adjust said ventricular pacing rate based on the correction            value (CV).

For instance, whether an atrial sense rate is valid can be identifiedaccording to the atrial rate and/or the atrial rate variability. In afirst example, a valid atrial sense rate is determined when the atrialsense rate derived from said sensing signal lies within a range for anormal atrial rate. For an adult at rest, the normal atrial rate rangesfrom 60 to 100 bpm, higher during exercise. However, the range maydeviate according to factors individual for the patient (age, diseases,medication, fitness level etc.). According to an embodiment, a validatrial sense rate is determined when the atrial rate variability iswithin a certain range indicating a regular atrial rhythm. Thevariability of the atrial rhythm can be determined via the difference oftime intervals between successive atrial events.

According to an embodiment, the processing circuitry is configured todetermine a ventricular pacing rate based on a calculated ventricularpacing rate in case no valid atrial sense rate is determined.

According to an embodiment, an atrial sense rate is not valid if theatrial sense rate is outside the range of a normal atrial rate, or ifthe atrial rate variability is outside the range of a regular atrialrhythm. Alternatively, an atrial sense rate is not valid when no atrialevents are received via the reception device, or when the noise level ofthe sensing signal is too high, or when atrial sensing/detection of theleadless pacemaker device is inhibited.

In one aspect, a leadless pacemaker device configured to provide for anintra-cardiac pacing comprises a processing circuitry configured togenerate ventricular pacing signals for stimulating ventricular activityat a ventricular pacing rate, and a reception device for receiving asensing signal indicative of an atrial activity, wherein the processingcircuitry is configured to determine an atrial sense rate of atrialevents derived from said sensing signal, wherein the processingcircuitry is further configured to determine a correction value based ona difference between said ventricular pacing rate and said atrial asensing rate and to adjust said ventricular pacing rate based on thecorrection value.

The leadless pacemaker device is configured to generate and emit pacingsignals, the leadless pacemaker device being located in the right orleft ventricle such that at least one pacing electrode is in electricalcontact with cardiac tissue for injecting stimulation energy intocardiac tissue. Ventricular pacing signals are generally generated at aventricular pacing rate, wherein the ventricular pacing rate is adaptivebased on whether an atrial sense rate can be determined from a sensingsignal received via the reception device or not.

Herein, in case an atrial sense rate—which is indicative of a timingbetween atrial events derived from the sensing signal picked up by meansof the reception device—becomes available and suitable for a pacing, theventricular pacing rate is adapted based on a difference between theventricular pacing rate (as it has been used prior to picking up anatrial sense rate suitable for pacing) and the now detected atrial senserate. Based on the difference between the ventricular pacing rate andthe atrial sense rate a correction value is determined, and based on thecorrection value the ventricular pacing rate is adjusted.

By applying the correction value, in particular, the ventricular pacingrate is progressively adapted to come into synchrony with the atrialsense rate. The ventricular pacing rate hence is not promptly switchedto match the detected atrial sense rate, but is progressively adjustedso that it approaches and converges towards the atrial sense rate. Oncean atrial sense rate becomes available and usable for a pacing strategy,hence a progressive adjustment of the ventricular pacing rate isinitiated in order to bring the ventricular pacing rate into synchronywith the atrial sense rate.

By applying such correction value an adjustment similar to aphase-locked loop (PLL) mechanism is applied to progressively adjust theventricular pacing rate to an atrial sense rate in case an atrial senserate becomes available from the sense reception signal and is suitablefor pacing. By means of such phase-locked loop mechanism the correctionvalue is used to progressively adjust the ventricular pacing rate inorder to adapt the ventricular pacing rate until its phase issynchronized with the atrial sense rate (while taking an offsetdetermined by the atrioventricular (AV) delay into account), thecorrection value being adapted in a feedback loop until the phase of theventricular pacing rate is locked to the phase of the atrial sense rate.

In one embodiment, the processing circuitry is configured to determinean atrial interval indicative of a time interval between two successiveatrial events. From the atrial sensing signal picked up by means of thereception device, atrial events indicative of atrial activity due toatrial contractions are determined, the atrial interval indicating thetime between two successive atrial events. Generally, the ventricularinterval, i.e., the interval between two successive ventricular pacingsignals or intrinsic sense events, should match the atrial interval, theatrial sense rate being the inverse of the atrial interval and defininga quantity to which the ventricular pacing rate should be adapted forproviding for an atrioventricular synchronous pacing operation.

The processing circuitry may, in one embodiment, be configured todetermine a calculated ventricular-atrial delay indicative of a timedelay at which an atrial event is predicted to occur following a priorventricular pacing or sense event. The ventricular-atrial delay hereinmay for example be determined from a calculated atrial-ventricular delayand a current ventricular interval (indicative of a current timeinterval between two successive ventricular pacing signals).

The atrial-ventricular delay is the delay at which a ventricular sensesignal or pacing signal should ideally follow after an atrial event. Anoptimized value for the atrial-ventricular delay (in short AV delay) mayfor example be determined from the averaged measured atrial interval,wherein approaches are well-known to determine an optimalatrial-ventricular delay by for example measuring pulsed wave Doppler ofmitral inflow at varying AV delays or obtaining continuous wave Dopplervelocity-time integral (VTI) of aortic valve outflow at varying AVdelays. The calculated ventricular-atrial delay may be determined bysubtracting the value of the atrial-ventricular delay from theventricular interval.

The calculated ventricular-atrial delay indicates the predicted point intime at which a next atrial event should occur after a prior ventricularpacing or sensing event in case the ventricular rate is correctlysynchronized to the atrial sense rate. At the time of occurrence of aventricular event, i.e., the generation of a ventricular pacing signalor the sensing of an intrinsic ventricular sense signal, a timer isstarted and is used to measure how much time has elapsed since the lastventricular event. At the time of the next occurrence of an atrial eventthe time is stored to obtain a time value for a true time of occurrenceof an atrial event following the prior ventricular event, wherein thetrue time of occurrence may be set into relation with the calculatedventricular-atrial delay in order to determine the correction valuebased on such timing relation.

Moreover, according to an embodiment of the present invention, theprocessing circuitry is configured to determine a multiplicity of timebins and to evaluate into which time bin VA_(true) falls for determiningthe correction value (CV).

In one embodiment, based on the calculated ventricular-atrial delay amultiplicity of time bins may be determined, the time bins each beingdefined by a lower limit and an upper limit and being distributed intime around the calculated ventricular-atrial delay. The time bins aresequentially aligned, one time bin following the next, wherein a centraltime bin may be defined such that the ventricular-atrial delay fallsinto that central time bin.

Preferably, according to an embodiment, the processing circuitry isconfigured to determine a ventricular-atrial (VA) delay feedback value,wherein the VA delay feedback value is proportional to the differencebetween the calculated ventricular-atrial delay (VA_(calc)) andVA_(true), wherein the processing circuitry is configured to calculatethe correction value (CV) based on the VA delay feedback value.

Based on such time bins the correction value may be set in order toprogressively adapt the ventricular pacing rate to the atrial senserate. In particular, the processing circuitry may be configured toevaluate into which time bin the true time of occurrence falls fordetermining the correction value. For this, the true time of occurrenceis compared to the limits of each time bin, and if it is found that thetrue time of occurrence falls between the lower time limit and the uppertime limit of a particular time bin, it is identified that the time ofoccurrence falls into that time bin.

Each time bin herein, in one embodiment, is associated with a specificsetting value corresponding to a specific value of adjustment of theventricular pacing rate. For example, the central time bin into whichthe ventricular-atrial delay falls may have a setting value of 0,whereas earlier time bins may have progressively increasing settingvalues and later time bins may have progressively decreasing settingvalues.

Based on the finding into which time bin the true time of occurrence ofa detected atrial event falls, then, the correction value may be set tothe setting value of the corresponding time bin. If the true time ofoccurrence lies in the central time bin into which theventricular-atrial delay falls the correction value hence becomes 0,such that the ventricular pacing rate is not changed, assuming that aphase match between the ventricular pacing rate and the atrial senserate is already present. If the true time of occurrence falls into atime bin corresponding to a time range earlier than the calculatedventricular-atrial delay, the correction value assumes a positive valueto cause an increase of the ventricular pacing rate, the magnitude ofthe correction value herein becoming progressively larger the fartherthe time bin is located from the central time bin. If the true time ofoccurrence, in contrast, falls into a time bin corresponding to a timerange later than the calculated ventricular-atrial delay, the correctionvalue assumes a negative value to cause a decrease in the ventricularpacing rate, the magnitude of the correction value again becomingprogressively larger the farther the time bin is located from thecentral time bin.

By means of the correction value, hence, a progressive adjustment of theventricular pacing rate is applied. The number of time bins herein mayrange anywhere between two or three and a significantly larger number oftime bins. If, for example, three time bins are used, a central time binmay be associated with a setting value of 0, an earlier time binpreceding the ventricular-atrial delay may be associated with a positivesetting value and a later time bin may be associated with a negativesetting value.

Generally, by applying the correction value, the processing circuitry isconfigured to adjust the ventricular pacing rate to synchronize theventricular pacing rate with the atrial sense rate. Herein, for theadjustment, a first ramping function may be applied in order toprogressively adjust the ventricular pacing rate to the atrial senserate in case the atrial sense rate is suited for controlling aventricular pacing.

The first ramping function may provide for a linear ramping at apredefined ramping slope. The first ramping function however may alsoprovide for a nonlinear adjustment of the ventricular pacing rate.

In case the atrial sense rate can no longer be determined from thesensing signal picked up by means of the reception device, or in casethe atrial sense rate no longer is suited for controlling a ventricularpacing, no pacing according to atrial sense signals can or should beapplied. Generally, within a leadless pacemaker device placed in theventricle it may be difficult to reliably detect atrial signals, as theatrial signals occur in the far field and hence require for exampleelectrical far-field measurements or a sensing of mechanical signals,such as noise signals, acceleration signals or pressure signals stemmingfrom remote locations. Hence, atrial signals may be weak, such that anatrial sense rate may be lost. It in addition is possible that theatrial rhythm is not intact, because atrial contractions occur too slowor too fast. If atrial contractions are too far apart, this mayrepresent a failure in the intrinsic atrial sinus functionality, adevelopment of atrial fibrillation (which may make atrial sensesundetectable to the atrial event detection mechanism because of areduced signal amplitude), or a failure in the detection mechanism. Whenatrial contractions occur too fast, this may represent an atrialtachycardia or an intrinsic conduction disturbance associated withatrial extra-systoles. If the atrial rate is faster than the ventriclecan reliably keep up with, tracking the atrial rate may lead toinefficient ventricular pumping and/or ventricular fatigue, which is tobe avoided.

Hence, an atrial tracking involving an adjustment of the ventricularpacing rate to the atrial sense rate should only be initiated—even if anatrial sense rate is detectable—if the atrial sense rate is larger thana lower threshold and smaller than an upper threshold. In this case, theventricular pacing rate is progressively adapted to the atrial senserate. If this is not the case, because the atrial sense rate is smallerthan the lower threshold and hence too small, or because the atrialsense rate is larger than the upper threshold and hence too large, or ifthe atrial sense rate is not reliably detectable at all, the atrialtracking mode is, in one embodiment, disabled and no pacing according toatrial sense signals takes place.

In this case, it may be required to adjust the ventricle pacing rate toanother pacing strategy, for example to a rate response mechanismallowing for a variation of the ventricular pacing rate according to,e.g., physical activity of a patient. Hence, when disabling the atrialtracking mode, in one embodiment, the processing circuitry may beconfigured to adjust the ventricular pacing rate to synchronize theventricular pacing rate with a pacing rate defined by a rate responsivepacing algorithm according to a predefined second ramping function. Thesecond ramping function may then provide for a progressive adjustment ofthe ventricular pacing rate until it matches the pacing rate controlledand determined by the rate responsive pacing algorithm, i.e., a pacingby taking into account physical signals such as an accelerometer and/orother sensor signals signal indicative of patient activity.

The second ramping function may provide for a linear ramping at apredefined ramping slope. The second ramping function however may alsoprovide for a nonlinear adjustment of the ventricular pacing rate.

The leadless pacemaker device may provide for a continuous ventricularpacing at an adaptive ventricular pacing rate. In another embodiment,the leadless pacemaker device may be configured to provide a pacing inthe ventricle only if no intrinsic contraction signals in the ventricleat a suitable timing can be detected. Hence, in one embodiment, theprocessing circuitry is configured to generate a ventricular pacingsignal if no intrinsic ventricular sense signal is detected within apredefined time window following a prior ventricular event. If, instead,an intrinsic ventricular sense signal—over one or multiple cycles—isdetected within the predefined time window following the priorventricular event, no pacing signal is generated and injected, such thatin that case no pacing action takes place, but the pacemaker device isin an intrinsic conduction mode without providing an artificial pacing.

The leadless pacemaker device may comprise a housing and an arrangementof electrodes arranged on the housing for emitting pacing signals and,in addition, for receiving reception signals. The housing provides foran encapsulation of the leadless pacemaker device, the leadlesspacemaker device including all required components for autarkicoperation, such as the processing circuitry, an energy storage such as abattery, electric and electronic circuitry and the like, within thehousing. The housing is fluid-tight such that the leadless pacemakerdevice may be implanted into cardiac tissue and may be kept in cardiactissue over an extended period of time to provide for a long-time,continuous cardiac pacing operation.

In one aspect, the electrode arrangement comprises a first electrodearranged in the vicinity of a tip of the housing. The first electrodeshall come to rest on cardiac tissue in an implanted state of thepacemaker device, such that the first electrode contacts cardiac tissueat a location effective for injecting a stimulating signal into cardiactissue for provoking a pacing action, in particular a ventricularpacing.

In one aspect, the electrode arrangement comprises a second electrodeformed by an electrode ring circumferentially extending about thehousing. Alternatively, the second electrode may for example be formedby a patch or another electrically conductive area formed on thehousing. The second electrode is placed at a distance from the tip ofthe housing and hence at a distance from the first electrode arranged atthe tip.

In one embodiment, the housing comprises a far end opposite the tip, theelectrode arrangement comprising a third electrode arranged on thehousing at the far end opposite the tip. The third electrode isoperatively connected to the processing circuitry, such that theprocessing circuitry is enabled to receive and process signals receivedvia the third electrode.

In one aspect, the processing circuitry is configured to process, as areception signal indicative of atrial activity, a sense signal betweenthe first or the second electrode and the third electrode. Such signalvector arising between the first or second electrode and the thirdelectrode may be referred to as far-field vector, the first or secondelectrode and the third electrode exhibiting a rather large distancewith respect to each other such that a far-field differential signal maybe picked up at a reasonable signal-to-noise ratio.

According to an embodiment of the present invention, atrial events (As)and ventricular events (Vs) are sensed via the at least two of thefirst, second or third electrode.

The reception of atrial signals may take place by electricalmeasurements using electrodes of the electrode arrangement, suchelectrodes hence forming part of the reception device for receivingelectrical signals. Alternatively or in addition, the reception devicemay comprise a pressure sensor, a force sensor, a motion sensor or anoise sensor for sensing signals indicative of atrial activity. In suchcases atrial activity is not detected based on electrical measurements,but is picked up by signals having a mechanical origin.

At least the object is also addressed by means of a method for operatinga leadless pacemaker device configured to provide for an intra-cardiacpacing, the method comprising: generating, using a processing circuitry,ventricular pacing signals for stimulating ventricular activity,receiving, using a reception device, a sensing signal indicative of anatrial activity,

-   -   in case a valid atrial sense rate is determined,        -   determine a ventricular pacing rate according to the atrial            sense rate based on a calculated atrial-ventricular (AV)            delay,        -   generating ventricular pacing signals at the ventricular            pacing rate,        -   determine a calculated ventricular-atrial delay (VAcalc)            indicative of a time delay at which an atrial event (As) is            predicted to occur following a prior ventricular event (Vs),        -   measure a true occurrence of a time delay at which an atrial            event (As) occurs following a prior ventricular event (Vs)            (VAtrue) and determine a correction value (CV) based on a            timing relation between true occurrence of a time delay at            which an atrial event (As) occurs following a prior            ventricular event (Vs) (VAtrue) and the calculated            ventricular-atrial delay (VAcalc), and        -   adjust said ventricular pacing rate based on the correction            value (CV).

The advantages and advantageous embodiments described above for theleadless pacemaker device equally apply also to the method, such that itshall be referred to the above.

Additional features, aspects, objects, advantages, and possibleapplications of the present invention will become apparent from a studyof the exemplary embodiments and examples described below, incombination with the Figures and the appended claims.

DESCRIPTION OF THE DRAWINGS

The various features and advantages of the present invention may be morereadily understood with reference to the following detailed descriptionand the embodiments shown in the drawings. Herein,

FIG. 1 shows a schematic view of the human heart;

FIG. 2 shows a schematic view of a leadless pacemaker device;

FIG. 3 shows a schematic view of a leadless pacemaker device, indicatingsignal vectors between different electrodes of the leadless pacemakerdevice;

FIG. 4A shows a graphical representation of an intra-cardiac electrogram(IEGM);

FIG. 4B shows sequential diagram of atrial senses and ventricular paces;

FIG. 5 shows a portion of the intra-cardiac electrogram, illustratingthe adjustment of a ventricular rate according to an atrial sense rate;

FIG. 6 illustrates a schematic of an adjustment mechanism for adjustingthe ventricular pacing rate;

FIG. 7 illustrates an adjustment of the ventricular rate when switchingbetween different pacing modes;

FIG. 8A shows an intra-cardiac electrogram, prior to processing;

FIG. 8B shows a processed signal stream derived from the intra-cardiacelectrogram to derive atrial events;

FIG. 9 shows a portion of the processed signal to determinecharacteristic values from that signal for the determination of anatrial event;

FIG. 10 shows the establishment of windows around a calculatedventricular-atrial delay for determining whether a ventricular rate isin synchrony with an atrial sense rate;

FIG. 11 shows a flow diagram for switching between different modes of apacemaker device;

FIG. 12 shows a flow diagram for switching from a synchronous mode to anasynchronous mode; and

FIG. 13 shows a flow diagram for switching from an asynchronous mode toa synchronous mode.

DETAILED DESCRIPTION

Subsequently, embodiments of the present invention shall be described indetail with reference to the drawings. In the drawings, like referencenumerals designate like structural elements.

It is to be noted that the embodiments are not limiting for the presentinvention, but merely represent illustrative examples.

In the instant invention it is proposed to provide a leadless pacemakerdevice providing for an intra-cardiac pacing, in particular aventricular pacing.

FIG. 1 shows, in a schematic drawing, the human heart comprising theright atrium RA, the right ventricle RV, the left atrium LA and the leftventricle LV, the so-called sinoatrial node SAN being located in thewall of the right atrium RA, the sinoatrial node SAN being formed by agroup of cells having the ability to spontaneously produce an electricalimpulse that travels through the heart's electrical conduction system,thus causing the heart to contract in order to pump blood through theheart. The atrioventricular node AVN serves to coordinate electricalconduction in between the atria and the ventricles and is located at thelower back section of the intra-atrial septum near the opening of thecoronary sinus. From the atrioventricular node AVN the so-called HISbundle H is extending, the HIS bundle H being comprised of heart musclecells specialized for electrical conduction and forming part of theelectrical conduction system for transmitting electrical impulses fromthe atrioventricular node AVN via the so-called right bundle branch RBBaround the right ventricle RV and via the left bundle branch LBB aroundthe left ventricle LV.

In case of a block at the atrioventricular node AVN, the intrinsicelectrical conduction system of the heart H may be disrupted, causing apotentially insufficient intrinsic stimulation of ventricular activity,i.e., insufficient or irregular contractions of the right and/or leftventricle RV, LV. In such a case, a pacing of ventricular activity bymeans of a pacemaker device may be indicated, such pacemaker devicestimulating ventricular activity by injecting stimulation energy intointra-cardiac tissue, specifically myocardium M.

Within the instant text, it is proposed to use a leadless cardiacpacemaker device 1, as schematically indicated in FIG. 1 , for providingfor a ventricular pacing action.

Whereas common leadless pacemaker devices are designed to sense aventricular activity by receiving electrical signals from the ventricleRV, LV they are placed in, it may be desirable to provide for a pacingaction which achieves atrioventricular (AV) synchrony by providing apacing in the ventricle in synchrony with an intrinsic atrial activity.For such pacing mode, also denoted as atrial tracking, it is required tosense atrial activity and identify atrial events relating to atrialcontractions in order to base a ventricular pacing on such atrialevents.

Referring now to FIGS. 2 and 3 , in one embodiment a leadless pacemakerdevice 1 configured to provide for an intra-cardiac pacing, inparticular employing an atrial tracking, comprises a housing 10enclosing electrical and electronic components for operating theleadless pacemaker device 1. In particular, enclosed within the housing10 is a processing circuitry 15, comprising for example also acommunication interface for communicating with an external device, suchas a programmer wand. In addition, electrical and electronic componentssuch as an energy storage in the shape of a battery are confined in thehousing 10. The housing 10 provides for an encapsulation of componentsreceived therein, the housing 10 having the shape of, e.g., acylindrical shaft having a length of for example a few centimeters.

The leadless pacemaker device 1 is to be implanted on intra-cardiactissue M first. For this, the leadless pacemaker device 1 comprises, inthe region of the tip 100, a fixation device 14 for example in the shapeof nitinol wires to engage with intra-cardiac tissue M for fixedlyholding the leadless pacemaker device 1 on the tissue in an implantedstate.

The leadless pacemaker device 1 does not comprise leads, but receivessignals relating to a cardiac activity, in the illustrated embodiment,by means of an electrode arrangement arranged on the housing 10 and alsoemits stimulation signals by means of such electrode arrangement. In theembodiment of FIGS. 2 and 3 , the leadless pacemaker device 1 comprisesdifferent electrodes 11, 12, 13 making up the electrode arrangement andserving to emit pacing signals towards intra-cardiac tissue M forproviding a pacing and to sense electrical signals indicative of acardiac activity, in particular indicative of atrial and ventricularcontractions.

A first electrode 11 herein is denoted as pacing electrode. The firstelectrode 11 is placed at a tip 100 of the housing 10 and is configuredto engage with cardiac tissue M.

A second electrode 12 serves as a counter-electrode for the firstelectrode 11, a signal vector P arising between the first electrode 11and the second electrode 12 providing for a pacing vector for emittingpacing signals towards the intra-cardiac tissue M.

In addition, the second electrode 12 may serve as a sensing electrodefor sensing signals, in particular relating to ventricular contractions,a signal vector V arising between the second electrode 12 and the firstelectrode 11, the signal vector V being denoted as near-field vector.

The second electrode 12 is placed at a distance from the first electrode11 and for example has the shape of a ring extending circumferentiallyabout the housing 10. The second electrode 12 is for example placed at adistance of about 1 cm from the tip 100 of the housing 10 at which thefirst electrode 11 is placed.

The leadless pacemaker device 1, in the embodiment of FIGS. 2 and 3 , inaddition comprises a third electrode 13 placed at a far end 101 of thehousing 10, the third electrode 13 serving as a sensing electrode forsensing signals indicative of cardiac activity in the far-field. Inparticular, a signal vector A arises between the third electrode 13 andthe first electrode 11, the signal vector A picking up signals beingindicative for example of atrial contractions and being denoted asfar-field vector.

The electrodes 11, 12, 13 are in operative connection with theprocessing circuitry 15, the processing circuitry 15 being configured tocause the first electrode 11 and the second electrode 12 to emit apacing signal for providing a stimulation at the ventricle. Theprocessing circuitry 15 furthermore is configured to process signalsreceived via the electrodes 11, 12, 13 to provide for a sensing ofcardiac activity, in particular atrial and ventricular contractions.

In order to provide for a pacing in the ventricle in which the leadlesspacemaker device 1 is placed, in particular to enable a pacing using anatrial tracking, a sensing of atrial activity is required to provide fordetected atrial sense markers in order to time a pacing in the ventriclein atrioventricular (AV) synchrony. For this, a far-field signal from inparticular the right atrium RA (see FIG. 1 ) shall be sensed in order toallow for a synchronous pacing in the right ventricle RV by means of theleadless pacemaker device 1 being implanted on intra-cardiac tissue M inthe right ventricle RV.

Generally, when a competent sinus rhythm is available, it is preferableto use such sinus rhythm in order to time a ventricular pacing based onthe sinus rhythm. Because the pacemaker device 1 is placed in theventricle, however, signals allowing for a detection of an atrial senserate being indicative of intrinsic atrial activity may not always bereliably available because received signals may be low in amplitude. Inaddition, a pacing in the ventricle based on and in synchrony withatrial signals is potentially not suitable if a detected atrial senserate is too slow or too fast. If atrial events detected based on asignal received from the atrium are too far apart, this may represent afailure of the intrinsic atrial sinus functionality, a development ofatrial fibrillation, or a failure in the detection mechanism. If incontrast atrial events are too close together, this may represent anatrial tachycardia or an intrinsic conduction disturbance associatedwith atrial extrasystoles, in which case the atrial sense rate may betoo fast for the ventricle and an atrial tracking should be avoided inorder to prevent an inefficient ventricular pumping or ventricularfatigue.

Hence, a switching between an atrial tracking mode and a mode in whichthe atrial tracking is disabled may be required. In the atrial trackingmode the pacing in the ventricle takes place based on a detected atrialsense rate. In contrast, if the atrial tracking mode is disabled theventricular pacing takes place by employing another mechanism, such as arate response mechanism in which the ventricular pacing rate is governedand varies for example in dependence on a detected physical activity ofa patient, which may for example be derived from sensor readings such asaccelerometer readings or the like.

In general, if the atrial sense rate is too small or too large (i.e.,the atrial sense rate is smaller than a lower threshold or larger thanan upper threshold), or if no reliable atrial sense rate can be derivedfrom atrial signal, an atrial tracking mode should be disabled. Instead,if an atrial sense rate can be reliably detected because atrial eventsare continuously received and allow to determine a stable atrial rate,and if in addition the atrial sense rate is in between the lowerthreshold and the upper threshold, the atrial tracking mode should beenabled.

If the atrial tracking mode is enabled, the ventricular pacing rateshould be adapted to the atrial sense rate. Herein, prior to enablingthe atrial tracking mode the ventricular pacing rate has been controlledaccording to another mechanism and hence may substantially differ fromthe now available atrial sense rate, such that the enabling of theatrial tracking mode involves a control of the ventricular pacing ratesuch that it now takes account of the atrial sense rate.

In order to avoid a sudden switching from one ventricular pacing rate toanother at the time of enabling the atrial tracking mode, it herein isproposed to progressively adjust the ventricular pacing rate such thatit is progressively adapted to resemble and follow the atrial senserate. The progressive adjustment may take into account programmed attackand decay limits such that a slope of the adaption of the ventricularpacing rate does not exceed predefined limits.

In one embodiment, the adjustment of the ventricular pacing rate towardsthe now available atrial sense rate may follow the principles of aphase-locked loop, the control mechanism being such that a correctionvalue is determined according to a difference between a phase of theatrial sense rate and the current ventricular pacing rate, thecorrection value being then used to correct the ventricular pacing ratesuch that it is adjusted towards the atrial sense rate.

In one embodiment, when switching to the atrial tracking mode, an(ideal) atrioventricular delay AV, as illustrated in FIG. 4A accordingto an example of an intra-cardiac electrogram IEGM, is determined. Thecalculation of the atrioventricular delay AV may for example make use ofan average of an atrial interval TA between two successive atrial eventsAs, the average for example being taken over multiple cycles. Theaveraged atrioventricular delay AV may then be used, together with thecurrent interval of the ventricular pacing TV, to calculate aventricular-atrial delay VA being indicative of a predicted time atwhich an atrial event As should follow a ventricular pacing or senseevent Vs (if the ventricular pacing rate and the atrial sense rate arein synchrony.

FIG. 4B shows schematically a sequence 41 of atrial sensed events As andthe sequence 42 of ventricular paced events Vp according to the atrialsensed events. According to an aspect of the invention, the ventricularpacing rate can be changed to match the atrial sense rate. The atrialpacing rate in sequence 41 of FIG. 4B amounts 60 bpm due toatrial-to-atrial intervals of 1000 ms. Via changing the ventricularpacing rate by a small amount in one cardiac cycle and then returning tothe previous rate in the next cycle, the phase relationship of the paceinterval and the atrial interval can be adjusted. For example, if theatrial rate is 60 bpm as in sequence 41, and the ventricular pacing rateis 60 ppm, the time duration between the atrial sense and theventricular pace may be, say, 180 ms (43 in FIG. 4B). If it is desiredto adjust the AV delay instead to 200 ms, it is possible to generate alonger ventricular-to-ventricular pacing interval for one cycle (44 inFIG. 4B) and then set the ventricular-to-ventricular interval intervalback to 1000 ms (cycle 45 in FIG. 4B) in order to achieve a temporalshift the Vp with respect to the As. If the AV delay is measured everycycle and compared to the desired delay, such small corrections can beused to continuously keep the AV delay at the proper value even if theatrial rate drifts up and down. A side effect is that the ventricularrate will track the drift in the atrial rate.

Based on the calculated ventricular-atrial delay VA_(calc) as indicatedin FIG. 5 , and based on a measurement of the true time of occurrence ofthe next atrial event As following a ventricular pacing or sense eventVs, a correction of the ventricular pacing rate may be performed.

In particular, at the time of a ventricular event Vx (which may be apacing event Vp or which may be an intrinsic ventricular sense event Vs)a timer is started. At the time of the next atrial event As the timertime TT is stored such that the true time of occurrence of the atrialevent As following the prior ventricular event Vs is obtained.

The true time of occurrence of the atrial event As may now be comparedto the calculated ventricular-atrial delay VA_(calc), and from suchcomparison a correction value may be determined.

In particular, in one embodiment, as illustrated in FIG. 5 a number oftime bins B⁻³ . . . B₊₂ may be defined, the time bins B⁻³ . . . B₊₂being distributed around the calculated ventricular-atrial delayVA_(calc) such that a central time bin B₀ contains the calculatedventricular-atrial delay VA_(calc), i.e., the predicted time ofoccurrence of the atrial event As if the ventricular rate and the atrialsense rate were in synchrony.

Each time bin B⁻³ . . . B₊₂ herein is bounded by a lower bound L₁ . . .L₆ and an upper bound L₂ . . . L₇, the time bins B⁻³ . . . B₊₂ havingfor example identical widths.

Each time bin B⁻³ . . . B₊₂ is associated with a particular settingvalue. The central time bin B₀ has a setting value of 0. The time binsB⁻³ . . . B⁻¹ preceding the central time bin B₀ have a positive settingvalue, whereas the time bins B₊₁, B₊₂ succeeding the central time bin B₀have a negative setting value.

Based on the measured true time of occurrence of the atrial event As itis now determined into which time bin B⁻³ . . . B₊₂ the atrial event Asfalls. The correction value is then set according to the setting valueof the corresponding time bin B⁻³ . . . B₊₂. If the atrial event Asfalls into the central time bin B₀, the correction value hence is set to0. If the atrial event As falls into a time bin B⁻³ . . . B⁻¹ precedingthe central time bin B₀, the correction value is set to a positive valueaccording to the specific setting value of the time bin B⁻³ . . . B⁻¹the true time of occurrence of the atrial event As falls into, whereinthe setting values of the time bins B⁻³ . . . B⁻¹ progressively increasethe farther away the time bin B⁻³ . . . B⁻¹ is from the central time binB₀. If the atrial event As falls into a time bin B₊₁, B₊₂ succeeding thecentral time bin B₀, the correction value is set to a negative valueaccording to the specific setting value of the time bin B₊₁, B₊₂ thetrue time of occurrence of the atrial event As falls into, the magnitudeof the setting value of the time bin B₊₁, B₊₂ again increasing thefarther the time bin B₊₁, B₊₂ is away from the central time bin B₀.

A positive correction value causes an increase in the ventricular pacingrate such that the ventricular pacing takes place at a faster rate. Anegative correction value causes a reduction in the ventricular pacingrate such that the ventricular pacing is slowed down. In the instantembodiment, because the correction value is progressively set based on adifference between the ventricular rate and the atrial sense rate,determined by comparing a true time of occur of occurrence of an atrialevent As (following a prior ventricular event Vs) with a predicted timeof occurrence (represented by the calculated ventricular-atrial delayVA_(calc)), the ventricular pacing rate is progressively changed untilit has converged to the atrial sense rate, hence avoiding a suddenswitching between distinct ventricular pacing rates when switching fromone pacing mode to another.

The principle of adjusting the ventricular pacing rate when enabling theatrial tracking mode (and likewise when disabling the atrial trackingmode causing a switch to another pacing mode) may be compared with aphase-locked loop technique, as it is generally illustrated in FIG. 6 .

Within such technique, an input I, namely in the instant case the atrialsense rate, is compared in a comparator 150 to an output rate O, in theinstant case the ventricular pacing rate. The comparator 150 inparticular determines a difference in the phase between the input rateI, namely the atrial sense rate, and the output rate O, namely theventricular pacing rate, and provides the difference towards a filteringunit 151 which may provide for a filtering in order to improve stabilityof the control mechanism. The filtered difference is then forwarded toan adjustment unit 152 which, according to the difference, determines acorrection value for correcting the output rate O, namely theventricular pacing rate, and adjusts the output rate O accordingly. Thenow corrected output rate O, namely the ventricular pacing rate, is fedback to the input, such that a feedback mechanism is provided forprogressively adjusting the output rate O, namely the ventricular pacingrate, according to an input rate I, namely the atrial sense rate.

The adjustment of the ventricular pacing rate hence takes placeaccording to predefined attack and decay limits for a rate of changesuch that the change in the ventricular pacing rate takes placeprogressively. This is illustrated in FIG. 7 .

Herein, prior to a time T1 the ventricular pacing rate is controlledaccording to a pacing mechanism other than an atrial tracking. Theventricular pacing rate may, for example, be controlled according to arate response mechanism in which the ventricular pacing rate is variedaccording to a physical activity of a patient to assume a rate responserate FR, such that the ventricular pacing rate is reduced in times ofinactivity, for example, during sleep, and is increased in times ofheavy activity, for example during heavy physical exercise.

Prior to time T1 no atrial sense rate is available or suitable forpacing. At time T1 a suitable atrial sense rate FA becomes available,such that the pacemaker device 1 switches to an atrial tracking mode inwhich the ventricular pacing rate is controlled according to a detectedatrial sense rate FA.

In a first phase, herein, between times T1 and T2 the ventricular pacingrate is ramped up according to a ramping function R1 until it is insynchrony with the atrial sense rate FA at time T2 and from that time onis controlled in synchrony with the atrial sense rate FA. The rampingfunction R1 is defined by the progressive adjustment of the ventricularrate using an iterative application of suitable correction values asdescribed, for one embodiment, above.

At time T3 a suitable atrial sense rate no longer is available, eitherbecause of an undersensing of atrial signals or because the atrial senserate has become too small or too high. In that case the pacemaker device1 switches back to another pacing mode, for example to a pacing modemaking use of a rate response mechanism. Again, in order to avoid asudden switching of the ventricular pacing rate, the ventricular pacingrate is progressively adapted by applying a ramping function R2 until ithas converged towards the rate response rate FR.

For the switching back to the rate response rate FR a similar mechanismas for the switching to synchronize with the atrial sense rate may beapplied.

The ventricular pacing may be continuous such that a pacing signal isgenerated and injected into cardiac tissue independent of intrinsicventricular activity. Alternatively, intrinsic signals may be sensed andtaken into account in order to avoid a ventricular pacing in caseintrinsic ventricular signals are present. For this, at each ventricularevent Vs, may it be a ventricular pacing event or a ventricular senseevent due to intrinsic ventricular activity, a ventricular pacing ratetimer may be started, the timer defining a maximum time until which anintrinsic ventricular event must occur in order to avoid a ventricularpacing signal. If the timer has not timed out when an intrinsicventricular event Vs is detected, the generation of a ventricular pacingsignal is skipped. If the timer does timeout, a ventricular pacingsignal is generated and injected.

As illustrated above according to FIGS. 2 and 3 , for detecting atrialsignals to derive an atrial sense rate, beneficially a far-field vectorin between electrodes 11, 13 being farthest away on the housing 10 ofthe pacemaker device 1 is used. Such large vector is preferred in orderto accentuate variations in the electromagnetic field paths from theright atrial tissue to the electrodes 11, 13, allowing for a detectionof a differential signal indicative of atrial activity.

The measured signal should be filtered in order to differentiate atrialsignals from other signals, in particular ventricular signals, and ablanking mechanism may in addition be employed to blank out signals notrelated to atrial activity.

This is illustrated, in an example, in FIGS. 8A and 8B, illustrating anintra-cardiac electrogram IEGM measured in the ventricle prior tofiltering and blanking (FIG. 8A) and after filtering and blanking (FIG.8B). In particular, a blanking window T_(blank) may be employed to blankout such periods of the signals which may relate to activity in theheart other than atrial activity.

The processed and filtered signal is then used to determine atrialevents As.

Atrial events As may in particular be determined by employing aprocessor or state-machine logic. In particular, for determining anatrial event Vs a signal may be analyzed, as illustrated in FIG. 9 , fordetermining a maximum positive peak PP, a maximum negative peak PN, anaverage value AP of positive signal portions above a baseline B, and anaverage value AN of negative portions below the baseline B. An atrialevent As may then for example be determined according to a crossing of athreshold D, wherein one or multiple thresholds may be employed, forexample a positive threshold and a negative threshold, the thresholdsbeing for example calculated according to the characteristics determinedfrom the processed signal.

Generally, if intrinsic ventricular activity is present, beneficiallysuch intrinsic signals should not be interrupted by an artificialpacing, dependent on however whether the intrinsic ventricular activityis in synchrony with atrial activity. If a synchronous intrinsicventricular activity is present, the pacemaker device 1 should beoperated in an intrinsic conduction mode in which the heart operatesnaturally making use of its intrinsic conduction mechanism.

In the intrinsic conduction mode the pacemaker device 1 observesventricular activity in particular with respect to its synchrony withatrial activity. For this, time windows W1, W2 as illustrated in FIG. 10may be established in order to monitor the time duration between aventricular event Vs and a following atrial event As.

The windows W1, W2 herein may be established based on a calculatedventricular-atrial delay VA_(calc) as referred to above (see inparticular FIGS. 4 and 5 and the corresponding description), thecalculated ventricular-atrial delay VA_(calc) indicating the time atwhich an atrial event As should follow a prior ventricular event Vs ifthe ventricular rate and the atrial rate are in synchrony.

The windows W1, W2 in particular may be centered about theventricular-atrial delay VA_(calc), wherein at each intrinsicventricular event Vs a timer is started and a true time of occurrence ofan atrial event As (timer time TT) is determined and stored. If the truetime of occurrence of the atrial event As falls into the inner windowW1, it is assumed that the ventricular rate and the atrial rate are insynchrony, and the pacemaker device remains in the intrinsic conductionmode, hence not providing any artificial pacing.

If the true time of occurrence of the atrial event As, instead, isoutside the inner window W1, but still falls within the outer, widerwindow W2 (also referred to as drift window) it is assumed thatatrioventricular synchrony is lost. The processing circuitry 15 of thepacemaker device 1 hence switches into an atrial tracking mode andcontrols the ventricular rate by generating and injecting pacingsignals. For adjusting the ventricular pacing rate to the atrial senserate, herein, an algorithm as described above according to FIG. 5 may beemployed, hence adjusting the ventricular pacing rate analogously to aphase-locked loop control.

If a predetermined number of consecutive ventricular senses occurs insynchrony with the atrial rate, the control logic may switch back to theintrinsic conduction mode.

If within the windows W1, W2 no atrial events As occur, the controllogic of the processing circuitry 15 may switch to a searching mode inwhich it is searched for atrial events As. Within such searching modethe ventricular rate may be controlled according to another pacingmechanism, such as a rate response mechanism, wherein the ventricularpacing rate may be progressively adjusted to approach the rate ascontrolled by the rate response mechanism.

A search for atrial events As is initiated when the processing circuitry15 is in the searching mode. In the searching mode the processingcircuitry 15 may analyze an intra-cardiac electrogram reading forpotential atrial events and may determine characteristic values such aspeak values and average values to evaluate potential candidates foratrial events. Bandpass filters may be employed to cover a frequencyrange of a supported atrial sensing, wherein frequencies may be sortedinto a continuous range of filter bins. A digital data stream which isanalyzed by the processing circuitry may feed into such filter bins,wherein threshold detectors may be enabled at the output of each filter(except the filter that covers the rate interval that corresponds withthe current ventricular rate). The threshold value employed by thethreshold detectors may be a common value that can be controlled by thesearch algorithm. The threshold value herein may be raised or lowereduntil just one detector is active during a predetermined number ofconsecutive ventricular cycles. An interval associated with thisdetector is then used to reload a ventricular timer at each ventricularevent Vs. If this results in stable candidate atrial events within thecalculated ventricular-atrial delay VA_(calc), it is assumed that anatrial sense rate now again is picked up and the control logic mayswitch back to the intrinsic conduction mode or to the atrial trackingmode. If in contrast within the calculated ventricular-atrial delayVA_(calc) no stable candidate atrial event As is detected, the searchcircuitry may be disabled to save power, and pacing continues forexample according to a rate response mechanism.

If a search has not been successful in identifying stable atrial eventsAs, a predetermined search delay may be initiated for temporarily pausesearching. The control logic, during the search delay, uses an adaptiverate according to the rate response mechanism to reload the ventriculartimer, and at the end of the search delay the search circuitry may beenabled again to perform another search. This may repeat indefinitely aslong as no stable candidate atrial events As are detected and hence noreliable atrial sense rate is picked up.

Between searches, the control logic may monitor for consistent candidateatrial events As within the ventricular-atrial delay window (window W1in FIG. 10 ), and if stable atrial events As are detected, the controllogic switches back to the intrinsic conduction mode.

The switching between different modes is illustrated, according to anembodiment, in FIG. 11 . If an atrial sense rate is detected and is insynchrony with a ventricular rate of intrinsic ventricular event Vs, thepacemaker device 1 is in the intrinsic conduction mode S1. If synchronyis lost because the ventricular rate and the atrial rate drift out ofsynchrony, the pacemaker device 1 switches into the tracking mode S2. Ifeither in the intrinsic conduction mode S1 or the tracking mode S2 nostable atrial senses allowing for a detection of an atrial sense rateare available, the device switches into the searching mode S3. If asearch is performed, but is not successful in identifying stable atrialevents As, the device may switch into a delay mode S4 in which a searchis paused and a search circuitry is powered off an order to save energy,until at the end of the search delay the device switches back to thesearching mode S3. If again a reliable atrial sense rate in synchronywith a ventricular rate is detected, the device switches back to theintrinsic conduction mode S1 (or, if the atrial sense rate is not insynchrony with the ventricular rate, to the tracking mode S2).

A general schematic of the switching between an atrioventricularsynchronous mode, involving an atrial tracking, and an asynchronous modeis illustrated in FIGS. 12 and 13 .

In the synchronous mode an atrial tracking is employed, the ventricularpacing rate hence following the intrinsic atrial sense rate. If, in thesynchronous mode (state N1 in FIG. 12 ), atrial features are detectedand an atrial sense rate hence is reliably picked up, the device remainsin the synchronous mode (state N2). If instead no atrial event As isdetected, it may be checked whether an atrial event As cannot bedetected for a predetermined number of cycles N_(asynch), for example 10consecutive cycles. If indeed no atrial event As can be detected forsuch predetermined number of cycles N_(asynch) (state N3), it isswitched to the asynchronous pacing mode (state N4). If atrial events Asare again picked up prior to reaching the predefined number ofconsecutive cycles N_(asynch) in state N3, the device remains in thesynchronous mode (state N5).

If the device is in the asynchronous mode (state M1 as illustrated inFIG. 13 ), it is checked whether an atrial feature As is detected. Ifthis is the case, it may be checked if atrial events As can be stablydetected for a predetermined number of cycles N_(synch), for example 10cycles (state M2). If this is the case, it is switched to thesynchronous mode (state M3).

If in state M1 no atrial features are detected, the device remains inthe asynchronous pacing mode (state M4). If in state M2 stable atrialevents As cannot be detected for the predetermined number of cyclesN_(synch), the device also remains in the asynchronous pacing mode(state M5).

The predetermined number of cycles N_(asynch) for switching to theasynchronous mode (state N3 in FIG. 12 ) and the predetermined number ofcycles N_(synch) for switching from the asynchronous mode to thesynchronous mode (state M2 in FIG. 13 ) may be equal or may differ fromeach other. The predetermined number of cycles N_(asynch), N_(synch) maybe for example 10, but may also be larger or smaller.

Algorithms and procedures to control a pacing rate and to switch fromone mode to another are implemented in the processing circuitry 15 ofthe pacemaker device 1 for example by software run on one or multiplesuitable processors.

It will be apparent to those skilled in the art that numerousmodifications and variations of the described examples and embodimentsare possible in light of the above teaching. The disclosed examples andembodiments are presented for purposes of illustration only. Otheralternate embodiments may include some or all of the features disclosedherein. Therefore, it is the intent to cover all such modifications andalternate embodiments as may come within the true scope of thisinvention, which is to be given the full breadth thereof. Additionally,the disclosure of a range of values is a disclosure of every numericalvalue within that range, including the end points.

LIST OF REFERENCE NUMERALS

1 Leadless pacemaker device

10 Housing

100 Tip

101 Far end

11 First electrode (pacing electrode)

12 Second electrode (pacing ring)

13 Third electrode

14 Fixation device

15 Processing circuitry

150 Comparator

151 Filtering unit

152 Adjustment unit

A Atrial vector

AN Negative average

AP Positive average

As Atrial event

AV Atrial-ventricular delay

AVN Atrioventricular node

B Baseline

B₀, B⁻¹, B⁻², B⁻³, B₊₁, B₊₂ Time bin

CV Correction value

D Threshold value

FA Atrial rate

FR Rate response rate

FV Ventricular rate

H HIS bundle

L1-L7 Limit

LA Left atrium

LBB Left bundle branch

LV Left ventricle

M Intra-cardiac tissue (myocardium)

P Pacing vector

PN Negative peak value

PP Positive peak value

R1, R2 Ramping function

RA Right atrium

RBB Right bundle branch

RV Right ventricle

S1-S4 Modes

T1-T4 Time

TA Atrial interval

TV Ventricular interval

T_(blank) Blanking window

TT Timer time

SAN Sinoatrial node

V Ventricular vector

VA Ventricular-atrial delay

VA_(calc) Calculated ventricular-atrial delay

Vs Ventricular event

W1, W2 Window

1. A leadless pacemaker device configured to provide for anintra-cardiac pacing, the leadless pacemaker device comprising: aprocessing circuitry configured to generate ventricular pacing signalsfor stimulating ventricular tissue, and a reception device for receivinga sensing signal indicative of an atrial activity, wherein theprocessing circuitry is configured to detect an atrial event derivedfrom said sensing signal, wherein the atrial event is a valid atrialsense event, where a series of atrial events lie within a range for anormal atrial rate, and/or when the atrial rate variability is within acertain range indicating a regular atrial rhythm, wherein in case avalid atrial sense event is detected, the processing circuitry isfurther configured to: determine a ventricular pacing event according tothe atrial event based on a calculated atrial-ventricular (AV) delay,determine a calculated ventricular-atrial delay (VA_(calc)) indicativeof a time delay at which an atrial event (As) is predicted to occurfollowing a prior ventricular event (Vs), measure a true occurrence of atime delay (VA_(true)) at which an atrial event (As) occurs following aprior ventricular event (Vs) and determine a correction value (CV) basedon a timing relation between VA_(true) and the calculatedventricular-atrial delay (VA_(calc)), and adjust said ventricular pacingtiming based on the correction value (CV).
 2. The leadless pacemakerdevice of claim 1, wherein in case no valid atrial sense event isdetected, the processing circuitry is configured to determine aventricular pacing event based on a calculated ventricular pacing event.3. The leadless pacemaker device of claim 1, wherein the processingcircuitry is configured to determine the calculated ventricular-atrialdelay (VA_(calc)) based on a calculated atrial-ventricular delay (AV)and a current ventricular interval (TV) indicative of a time intervalbetween two successive ventricular pacing signals.
 4. The leadlesspacemaker device of claim 1, wherein the processing circuitry isconfigured to determine a multiplicity of time bins (B₀, B⁻¹, B⁻², B⁻³,B₊₁, B₊₂) and to evaluate into which time bin (B₀, B⁻¹, B⁻², B⁻³, B₊₁,B₊₂) VA_(true) falls for determining the correction value (CV).
 5. Theleadless pacemaker device of claim 4, wherein each time bin (B₀, B⁻¹,B⁻², B⁻³, B₊₁, B₊₂) is defined by a lower time limit and an upper limit.6. The leadless pacemaker device of claim 4, wherein each time bin (B₀,B⁻¹, B⁻², B⁻³, B₊₁, B₊₂) is associated with a specific setting value,wherein the processing circuitry is configured to set the correctionvalue (CV) using the setting value of the time bin (B₀, B⁻¹, B⁻², B⁻³,B₊₁, B₊₂) VA_(true) falls in.
 7. The leadless pacemaker device claim 4,wherein the processing circuitry is configured to increase a ventricularpacing rate, determined by a multitude of ventricular events, ifVA_(true) falls into a time bin (B₀, B⁻¹, B⁻², B⁻³, B₊₁, B₊₂) precedingthe end of the calculated ventricular-atrial delay (VA_(calc)), and todecrease the ventricular pacing rate if the true time of occurrencefalls into a time bin (B₀, B⁻¹, B⁻², B⁻³, B₊₁, B₊₂) succeeding the endof the calculated ventricular-atrial delay (VA_(calc)).
 8. The leadlesspacemaker device of claim 1, wherein the processing circuitry isconfigured to determine a VA delay feedback value, wherein the VA delayfeedback value is proportional to the difference between the calculatedventricular-atrial delay (VA_(calc)) and VA_(true), wherein theprocessing circuitry is configured to calculate the correction value(CV) based on the VA delay feedback value.
 9. The leadless pacemakerdevice of claim 7, wherein the processing circuitry is configured toadjust said ventricular pacing rate to synchronize with an atrial senserate, determined by a multitude of atrial events, according to apredefined first ramping function (R1) when the atrial sense rate issuited for pacing.
 10. The leadless pacemaker device of claim 9, whereinthe processing circuitry is configured to adjust said ventricular pacingrate to synchronize with a pacing rate defined by a rate responsivepacing algorithm according to a predefined second ramping function (R2)when the atrial sense rate is not suited for pacing.
 11. The leadlesspacemaker device of claim 1, wherein the processing circuitry isconfigured to generate a ventricular pacing signal if no intrinsicventricular sense signal is detected within a predefined time windowfollowing a prior ventricular event (Vs).
 12. The leadless pacemakerdevice of claim 1, wherein the reception device comprises at least twoelectrodes for receiving a sensing signal indicative of atrial activity.13. The leadless pacemaker device of claim 12, comprising a housinghaving a tip and a far end, wherein one electrode is arranged in thevicinity of the tip and another electrode is arranged in the vicinity ofthe far end.
 14. A method for operating a leadless pacemaker deviceconfigured to provide for an intra-cardiac pacing, comprising:generating, using a processing circuitry, at least one ventricularpacing signals for stimulating ventricular tissue, receiving, using areception device, a sensing signal indicative of an atrial activity,detecting an atrial event (As) derived from said sensing signal, whereinthe atrial event is a valid atrial sense event, where a series of atrialsense events lie within a range for a normal atrial rate, and/or whenthe atrial rate variability is within a certain range indicating aregular atrial rhythm, in case a valid atrial sense event is detected,determine a ventricular pacing event according to the atrial event basedon a calculated atrial-ventricular (AV) delay, determine a calculatedventricular-atrial delay (VA_(calc)) indicative of a time delay at whichan atrial event (As) is predicted to occur following a prior ventricularevent (Vs), measure a true occurrence of a time delay (VA_(true)) atwhich an atrial event (As) occurs following a prior ventricular event(Vs) and determine a correction value (CV) based on a timing relationbetween true occurrence of a time delay at which an atrial event (As)occurs following a prior ventricular event (Vs) (VA_(true)) and thecalculated ventricular-atrial delay (VA_(calc)), adjust said ventricularpacing timing based on the correction value (CV).